Clinical studies have shown a correlation between chronic low level lead in the blood of humans, especially children, and various behavioral deficits, including hyperactivity and learning difficulty in school. Although several types of changes in function and biochemistry of brain regions and subcellular systems have been described, the cellular neuronal dysfunctions induced by chronic lead exposure are not well understood, at least in part due to the complexity of the mammalian brain. I propose to use the pond snail Lymnaea stagnalis as a model system to study chronic lead effects in individual, repeatably identifiable neurons. I will study (l) uptake and retention of lead in various tissues; (2) effects on behavior; (3) effects on transmitter content of identifiable neurons; and (4) effects on electrophysiology of identifiable neurons. The major thrusts of the research will be, first, to identify changes in neuronal parameters in neurons from chronically lead-exposed snails as compared to controls, e.g., larger undershoot or longer duration of action potential, smaller synaptic potentials, etc. Second, specific ionic events underlying these changes will be sought, e.g., changes in equilibrium potentials, specific ion channel densities or kinetics, etc. The long term goal of the study will be to determine the changes in biophysical and behavioral dysfunction. Similar physiological analysis should prove feasible with other environmental neurotoxins. Once specific neuronal effects have been found in this model system, it should then be possible to determine if similar effects occur in the brains of mammals. Knowledge of the cellular mechanisms underlying the action of lead on neurons should also contribute to the determination of "safe" levels of lead exposure, as well as pointing the way to possible remedial treatments.